Leptin Receptor Metabolism Disorder in Primary Chondrocytes from Adolescent Idiopathic Scoliosis Girls.
Leptin Receptor Metabolism Disorder in Primary Chondrocytes from Adolescent Idiopathic Scoliosis Girls.
复制标题
青春期特发性脊柱侧凸女孩原代软骨细胞瘦素受体代谢紊乱
DOI：
10.3390/ijms17071160
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发表时间：
2016-07-20
影响因子：
5.6
通讯作者：
Zhang HQ
中科院分区：
文献类型：
--
作者：
Wang YJ;Yu HG;Zhou ZH;Guo Q;Wang LJ;Zhang HQ
研究青少年特发性脊柱侧凸（AIS）女孩的原代软骨细胞代谢活性低下的潜在机制; AIS是一种常见于女孩的脊柱变形疾病。AIS与比健康个体低的骨量和骨质减少相关。瘦素被证明在骨生长中起重要作用。它还可以调节软骨细胞的功能。在AIS患者中瘦素和Ob-R水平的变化已在几项研究中报道。外周瘦素信号传导障碍与软骨细胞异常之间的潜在机制尚不清楚;在AIS患者和对照组中评估以下参数：血清总瘦素水平;原代软骨细胞质膜中Ob-R表达; JAK 2和STAT 3磷酸化状态。然后，我们抑制溶酶体和蛋白酶体，敲低网格蛋白重链（CHC）表达的原代软骨细胞分离自女童AIS和评估Ob-R的表达。我们研究了瘦素联合溶酶体抑制剂或CHC敲低对从AIS患者获得的原代软骨细胞的影响;与对照组相比，AIS患者显示出相似的总血清瘦素水平，JAK 2和STAT 3磷酸化减少，小关节软骨基质合成减少。AIS组原代软骨细胞的代谢活性和Ob-R的膜表达低于对照组。溶酶体抑制增加了Ob-R的总含量，但对Ob-R的膜表达或瘦素对AIS原代软骨细胞的作用没有影响。CHC敲低上调膜Ob-R水平，增强瘦素对AIS原代软骨细胞的作用;在一些患有AIS的女孩中，软骨细胞对瘦素低敏感的潜在机制是由于受体内吞速率和新合成的受体插入膜之间的不平衡导致的质膜Ob-R表达降低。
To investigate the underlying mechanisms of low metabolic activity of primary chondrocytes obtained from girls with adolescent idiopathic scoliosis (AIS); AIS is a spine-deforming disease that often occurs in girls. AIS is associated with a lower bone mass than that of healthy individuals and osteopenia. Leptin was shown to play an important role in bone growth. It can also regulate the function of chondrocytes. Changes in leptin and Ob-R levels in AIS patients have been reported in several studies. The underlying mechanisms between the dysfunction of peripheral leptin signaling and abnormal chondrocytes remain unclear; The following parameters were evaluated in AIS patients and the control groups: total serum leptin levels; Ob-R expression in the plasma membrane of primary chondrocytes; JAK2 and STAT3 phosphorylation status. Then, we inhibited the lysosome and proteasome and knocked down clathrin heavy chain (CHC) expression in primary chondrocytes isolated from girls with AIS and evaluated Ob-R expression. We investigated the effects of leptin combined with a lysosome inhibitor or CHC knockdown in primary chondrocytes obtained from AIS patients; Compared with the controls, AIS patients showed similar total serum leptin levels, reduced JAK2 and STAT3 phosphorylation, and decreased cartilage matrix synthesis in the facet joint. Lower metabolic activity and lower membrane expression of Ob-R were observed in primary chondrocytes from the AIS group than in the controls. Lysosome inhibition increased the total Ob-R content but had no effect on the membrane expression of Ob-R or leptin’s effects on AIS primary chondrocytes. CHC knockdown upregulated the membrane Ob-R levels and enhanced leptin’s effects on AIS primary chondrocytes; The underlying mechanism of chondrocytes that are hyposensitive to leptin in some girls with AIS is low plasma membrane Ob-R expression that results from an imbalance between the rate of receptor endocytosis and the insertion of newly synthesized receptors into the membrane.